Regulation of Intestinal Glucose Absorption by Ion Channels and Transporters

Abstract

The absorption of glucose is electrogenic in the small intestinal epithelium. The major route for the transport of dietary glucose from intestinal lumen into enterocytes is the Na⁺/glucose cotransporter (SGLT1), although glucose transporter type 2 (GLUT2) may also play a role. The membrane potential of small intestinal epithelial cells (IEC) is important to regulate the activity of SGLT1. The maintenance of membrane potential mainly depends on the activities of cation channels and transporters. While the importance of SGLT1 in glucose absorption has been systemically studied in detail, little is currently known about the regulation of SGLT1 activity by cation channels and transporters. A growing line of evidence suggests that cytosolic calcium ([Ca(2+)]cyt) can regulate the absorption of glucose by adjusting GLUT2 and SGLT1. Moreover, the absorption of glucose and homeostasis of Ca(2+) in IEC are regulated by cation channels and transporters, such as Ca(2+) channels, K⁺ channels, Na⁺/Ca(2+) exchangers, and Na⁺/H⁺ exchangers. In this review, we consider the involvement of these cation channels and transporters in the regulation of glucose uptake in the small intestine. Modulation of them may be a potential strategy for the management of obesity and diabetes.

Keywords: Ca2+ channels; K+ channels; Na+/Ca2+ exchanger; Na+/H+ exchanger; Na+/glucose cotransporter; glucose transporter type 2; glucose uptake.

Figure 1

Absorption of digested food (glucose) from the intestinal lumen into the blood, and transportation of the absorbed nutrients via mesenteric circulation to target cells.

Figure 2

Schematic illustration of regulatory mechanisms of small intestinal glucose uptake by cation channels and transporters. Glucose absorption takes place in small intestinal villus cells by SGLT1, which is driven by active sodium extrusion via the basolateral Na⁺/K⁺ ATPase. When basolateral K⁺ channels are closed to depolarize the membrane voltage, the electrogenic transportation of glucose is blocked. Intestinal glucose absorption is also up-regulated by Ca²⁺-dependent apical GLUT2 insertion. The [Ca²⁺]_cyt is mainly excluded by NCX1 on the basolateral IEC. NHE3 suppresses SGLT1 and ultimately affects intestinal glucose absorption. Increased [Ca²⁺]_cyt through CaSR is combined with CaM as a complex, which modulates AMPK and further activates SGLT1 or GLUT2 to adjust small intestinal glucose absorption.